This invention relates to non-invasive measurement of glucose in a biological matrix and more particularly relates to such measurements employing visible or near infrared radiation.
Many diabetic patients rely on self-monitoring of blood glucose for the proper regulation of an insulin therapy. Diabetic patients would benefit from a device capable of providing continuous non-invasive monitoring of their blood glucose levels. In addition to eliminating pain or possible infection, such monitoring can provide complete information on the blood glucose changes occurring over a long period of time. This information would enable the patient to optimize insulin doses and improve metabolic control.
Current progress on development of non-invasive glucose monitors has been recently reviewed in an article entitled xe2x80x9cSpectroscopic and Clinical Aspects of Noninvasive Glucose Measurements,xe2x80x9d by O. S. Khalil, published in volume 45 of Clinical Chemistry, P. 165 (1999). According to Khalil, several research groups are trying to develop non-invasive glucose monitoring systems based on absorption measurements in the near infrared region, although none has been converted into a reliable glucose monitoring system. One of the main problems preventing such development is that the expected glucose absorption is very low as compared to other components in the tissue, such as water.
Previous known researchers have used a point illumination in conjunction with a spatially resolved diffuse reflectance technique. Using a point illumination, Heinemann and his coworkers have reported good correlation between the measured scattering coefficients and the blood glucose levels in thirty out of forty-one patients in their in vivo studies. These studies are reported in the following publications:
L. Heinemann and G. Schmelzeisen-Redeker, xe2x80x9cNoninvasive continuous glucose monitoring in type I diabetic patients with optical glucose sensors,xe2x80x9d Diabetologia 41, 848 (1998).
J. T. Bruulsema, M. Essenpreis, L. Heinemann, J. E. Hayward, M. Berger, F. A. Greis, T. Koschinsky, J. Sandahl-Christiansen, H. Orskov, T. J. Farrell, M. S. Patterson, and D. Bocker, xe2x80x9cDetection of changes in blood glucose concentration in vivo with spatially resolved diffuse reflectance,xe2x80x9d OSA TOPS on Biomedical Optical Spectroscopy and Diagnostics, Vol. 3, 2 (1996);
J. T. Bruulsema, J. E. Hayward, M., T. J. Farrell, M. S. Patterson, L. Heinemman, M. Berger, T. Koschinsky, J. Sandahl-Christiansen, H. Orskov, M. Essenspris, G. Schmelzeisen-Redeker, and D. Bocker xe2x80x9cCorrelation between blood glucose concentration in diabetics and noninvasively measured tissue optical scattering coefficient,xe2x80x9d Opt. Lett., 22, 190 (1997).
However, the approach of Heinemann et al. presents difficulties, such as the lack of sufficient sensitivity to resolve small changes in glucose level. In addition, the measurements were found to vary with locations and to drift with time. Local variation may be caused by heterogeneous distribution of light absorbing and light scattering structures in the tissue, whereas the time variation may be caused in part by changes in blood supply associated with heartbeats.
U.S. Pat. No. 5,551,422 (Simonsen et al., issued Sep. 3, 1996) discloses a method of spatially resolved reflectance for measurements of glucose and tissue by use of a point illumination. A line illumination arrangement was mentioned. However, the patent states that when the input irradiation site is in the form of a straight line, spatial resolution is lower, and the detection sensitivity becomes poor as compared to a point illumination. As a result, Simonson et al. discourage the use of a line illumination.
U.S. Pat. No. 5,782,755 (Chance et al., issued Jul. 21, 1998) discloses another variation of spatial resolved diffused reflectance for measurement of glucose in a biological system. Chance et al. use multiple spot light sources, such as flash bulbs, and a single detector. The light sources are spaced different distances along a single line from a detector and are sequenced at different time intervals to derive the spatial reflectance profiles.
The preferred embodiment is useful for non-invasive measurement of blood glucose of a subject. In such an environment, glucose in a tissue can be measured by illuminating with electromagnetic radiation a first portion of the surface of the subject comprising a geometric element defined by moving a point in a path. The illuminated first portion results in a part of the radiation being emitted from the surface in a second portion displaced from the first portion. The radiation emitted from at least part of the second portion is detected within a field of view to generate detection signals. A processor analyzes the detection signals to measure the blood glucose of the subject.
The foregoing techniques offer a number of advantages. Detection sensitivity can be improved substantially as compared to a point illumination. The foregoing techniques allow averaging of scattering events over a large area of tissue. Such averaging reduces any inhomogeneity of the scattering structure in the tissue and thus improves reproducibility and reliability of the measurements. In addition, the foregoing techniques permit measurements of radiation reflectance at a distance farther away from the illumination site than prior techniques. Since the effective average light penetration is expected to be deeper into the skin at a far distance, it permits interaction of the photon in depth where the glucose is expected to be more abundant. The interaction with a rich glucose region can further result in improved detection sensitivity compared to a point illumination. In addition, it is possible to obtain a response about an order of magnitude higher than the response expected by the absorption methods described by other known researchers in the field. By using these techniques, blood glucose concentration can be non-invasively measured with a degree of accuracy and economy previously unattained.